The proposed research is designed to allow understanding and parameterization of the individual HEME GROUP-PROTEIN INTERACTIONS IN HEMOPROTEINS, to allow assessment of current theories of cooperativity. Both thermodynamics and kinetic approaches will be used to separate and identify the functional significance of porphyrin. Protein non-bonded interactions, steric and electronic axial interactions, spin change induced proximal histidine interactions. Thermodynamic studies will focus on obtaining deltaG Denaturation as a function of heme group constitution, utilizing ligand and metal substitution to allow independent assessment of axial effects, spin effects, and prophyrin protein contacts in stabilizing hemoprotein structure. Kinetic studies will focus on ligand exchange reactions of Co (III) Hb, which is low spin regardless of axial ligation, so that the contribution of axial ligand changes to cooperativity may be evaluated in the absence of spin change. These studies may thus allow assessment of the role of various heme group-protein interactions in contributing to the functional behaviour of Hb, so that the nature of the Hb "Trigger" may be understood.